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首页> 外文期刊>Neuron >Wnt signals organize synaptic prepattern and axon guidance through the zebrafish unplugged/MuSK receptor.
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Wnt signals organize synaptic prepattern and axon guidance through the zebrafish unplugged/MuSK receptor.

机译:Wnt信号通过未插入斑马鱼/ MuSK受体的突触前突和轴突引导。

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摘要

Early during neuromuscular development, acetylcholine receptors (AChRs) accumulate at the center of muscle fibers, precisely where motor growth cones navigate and synapses eventually form. Here, we show that Wnt11r binds to the zebrafish unplugged/MuSK ectodomain to organize this central muscle zone. In the absence of such a zone, prepatterned AChRs fail to aggregate and, as visualized by live-cell imaging, growth cones stray from their central path. Using inducible unplugged/MuSK transgenes, we show that organization of the central muscle zone is dispensable for the formation of neural synapses, but essential for AChR prepattern and motor growth cone guidance. Finally, we show that blocking noncanonical dishevelled signaling in muscle fibers disrupts AChR prepatterning and growth cone guidance. We propose that Wnt ligands activate unplugged/MuSK signaling in muscle fibers to restrict growth cone guidance and AChR prepatterns to the muscle center through a mechanism reminiscent of the planar cell polarity pathway.
机译:在神经肌肉发育的早期,乙酰胆碱受体(AChRs)积聚在肌肉纤维的中心,恰好是运动生长锥导航并最终形成突触的位置。在这里,我们显示Wnt11r绑定到斑马鱼拔出/ MuSK ectodomain来组织此中央肌肉区。在没有这样一个区域的情况下,预先形成图案的AChR无法聚集,并且通过活细胞成像可以看到,生长锥从其中央路径偏离。使用诱导型未插入/ MuSK转基因,我们表明中枢肌肉区的组织对于神经突触的形成是必不可少的,但对于AChR的前期模式和运动生长锥引导至关重要。最后,我们表明,阻断肌纤维中的非规范性不规则信号破坏了AChR的构图和生长锥引导。我们建议Wnt配体激活肌肉纤维中的未插入/ MuSK信号传导,以通过使人联想到平面细胞极性途径的机制来限制生长锥引导和AChR前置模式到达肌肉中心。

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